A Study of MEHD7945A in Combination With Cisplatin and 5-Fluorouracil (5-FU) or Paclitaxel and Carboplatin in Participants With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN)

NCT01911598 | Completed Phase 1

• 2 other identifiers: GO289092013-001285-42
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 6

Brief Summary

This open-label, multicenter study will evaluate the safety, tolerability, and pharmacokinetics of MEHD7945A in combination with chemotherapy (either cisplatin plus 5-FU or carboplatin plus paclitaxel) in participants with previously untreated R/M SCCHN. There are two stages for each arm in this study: a Dose-limiting Toxicity (DLT)-evaluation stage (Stage I) and a cohort-expansion stage (Stage II). In Stage I, DLTs will be assessed during a DLT Assessment Window of 21 days (i.e., Cycle 1 Day 1 through Cycle 1 Day 21) for both arms. In Stage II, participants will be enrolled to further characterize the safety, pharmacokinetics, and anti-tumor activity of MEHD7945A in combination with cisplatin + 5-FU or carboplatin + paclitaxel at the identified recommended Phase II dose.

Conditions

Head and Neck Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With DLTs

  Cycle 1 Day 1 through Cycle 1 Day 21 (Cycle length = 3 weeks)

• Percentage of Participants with Adverse Events

  From Baseline until 45 days after last dose of study drug or until initiation of another anti-cancer therapy, withdrawal or lost to follow-up, whichever occurs first (up to approximately 3 years)

Secondary Outcomes (18)

• Area Under Concentration-Time Curve From Day 1 to 21 (AUC0-21d) of MEHD7945A

  Pre-infusion (0 hour), 30 minutes post-infusion (infusion duration=90 minutes) on Day 1 of Cycles 1, 2, 3, 4, 8; 4 hours post-infusion on Day 1 of Cycle 1; Days 2, 4, 8, 15 of Cycle 1 (each cycle = 3 weeks)

• Maximum Serum Concentration (Cmax) of MEHD7945A

  30 minutes and 4 hours post-infusion (infusion duration=90 minutes) on Day 1 of Cycle 1; 30 min post-infusion on Day 1 of Cycles 2, 3, 4, and 8 (each cycle = 3 weeks)

• Minimum Serum Concentration (Cmin) of MEHD7945A

  Pre-infusion (0 hour) on Day 1 of Cycles 1, 2, 3, 4, and 8 (each cycle = 3 weeks)

• Cmax of Cisplatin

  Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 1-2 hours) on Day 1 of Cycle 1 (Cycle length = 3 weeks)

• Area Under Concentration-Time Curve From 0 to 6 Hours (AUC0-6h) of Cisplatin

  Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 1-2 hours) on Day 1 of Cycle 1 (Cycle length = 3 weeks)

Study Arms (2)

A: MEHD7945A+ Cisplatin + 5-FU

EXPERIMENTAL

Participants with previously untreated R/M SCCHN will receive MEHD7945A 1650 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or protocol violation. Cisplatin will be administered as 100 milligrams per square meter (mg/m\^2) IV infusion on Day 1 of Cycles 1 to 6. 5-FU will be administered as 1000 mg/m\^2/day administered as continuous infusion over Days 1-4 of Cycles 1 to 6.

Drug: 5-FU; Drug: Cisplatin; Drug: MEHD7945A

B: MEHD7945A + Paclitaxel + Carboplatin

EXPERIMENTAL

Participants with previously untreated R/M SCCHN will receive MEHD7945A 1650 mg IV infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or protocol violation. Carboplatin will be administered at a dose to achieve an area under the curve (AUC) of 6 milligrams/milliliter/minute (mg/mL/min) as an IV infusion on Day 1 of Cycles 1 to 6. Paclitaxel will be administered as 200 mg/m\^2 IV infusion on Day 1 of Cycles 1 to 6.

Drug: Carboplatin; Drug: MEHD7945A; Drug: Paclitaxel

Interventions

5-FU DRUG

5-FU will be administered as per schedule specified in the respective arm.

A: MEHD7945A+ Cisplatin + 5-FU

Carboplatin DRUG

Carboplatin will be administered as per schedule specified in the respective arm.

B: MEHD7945A + Paclitaxel + Carboplatin

Cisplatin DRUG

Cisplatin will be administered as per schedule specified in the respective arm.

A: MEHD7945A+ Cisplatin + 5-FU

MEHD7945A DRUG

MEHD7945A will be administered as per schedule specified in the respective arms.

Also known as: Duligotuzumab

A: MEHD7945A+ Cisplatin + 5-FU; B: MEHD7945A + Paclitaxel + Carboplatin

Paclitaxel DRUG

Paclitaxel will be administered as per schedule specified in the respective arm.

B: MEHD7945A + Paclitaxel + Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed R/M SCCHN of mucosal origin (e.g., oral cavity, oropharynx, hypopharynx, larynx) that is not amenable to further curative local therapy (e.g., surgery, radiation including re-irradiation) (1L R/M)
• Participants with unknown primary SCCHN presumed to be of head and neck mucosal origin are eligible if they meet all other entry criteria
• For participants who present with de novo metastatic disease, no prior systemic chemotherapy is allowed
• For participants with recurrent SCCHN, prior systemic therapy is allowed if it was given as part of induction or definitive therapy. If participants have received prior combined chemo-radiation therapy, they must be off therapy for at least 3 months
• Consent to provide archival tumor tissue for biomarker testing
• Life expectancy greater than or equal to (\>/=) 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Disease that is measurable per modified RECIST v1.1
• Adequate bone marrow and organ function

You may not qualify if:

• Nasopharyngeal cancer
• Prior treatment with an investigational or approved agent for the purpose of inhibiting human epidermal growth factor receptor (HER) family members. This includes, but is not limited to, cetuximab, panitumumab, erlotinib, gefitinib, and lapatinib
• Prior treatment with an epidermal growth factor receptor (EGFR) inhibitor is allowed if it was administered as part of definitive therapy for locally advanced disease and completed/terminated \>/= 3 months before study enrollment
• Major surgical procedure within 4 weeks prior to Day 1
• Leptomeningeal disease as the only manifestation of the current malignancy
• Active infection requiring antibiotics
• Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs)
• Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
• Current severe, uncontrolled systemic disease
• History of cardiac heart failure of New York Heart Association Class II or greater or serious cardiac arrhythmia requiring treatment (except for atrial fibrillation and paroxysmal supraventricular tachycardia)
• History of myocardial infarction within 6 months prior to Cycle 1, Day 1, or history of unstable angina
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• History of bleeding diathesis or coagulopathy other than that due to anticoagulation therapy
• Clinically significant gastrointestinal (GI) bleeding within 6 months prior to Cycle 1, Day 1
• History of interstitial lung disease (ILD)

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (6)

University of Colorado Cancer Center Department of Hematology

Aurora, Colorado, 80045, United States

Location

University of Chicago; Hematology/Oncology

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital;Hematology/ Oncology

Boston, Massachusetts, 02114, United States

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Related Publications (1)

• Gerber DE, Infante JR, Gordon MS, Goldberg SB, Martin M, Felip E, Martinez Garcia M, Schiller JH, Spigel DR, Cordova J, Westcott V, Wang Y, Shames DS, Choi Y, Kahn R, Dere RC, Samineni D, Xu J, Lin K, Wood K, Royer-Joo S, Lemahieu V, Schuth E, Vaze A, Maslyar D, Humke EW, Burris HA 3rd. Phase Ia Study of Anti-NaPi2b Antibody-Drug Conjugate Lifastuzumab Vedotin DNIB0600A in Patients with Non-Small Cell Lung Cancer and Platinum-Resistant Ovarian Cancer. Clin Cancer Res. 2020 Jan 15;26(2):364-372. doi: 10.1158/1078-0432.CCR-18-3965. Epub 2019 Sep 20.

  PMID: 31540980 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Fluorouracil; Carboplatin; Cisplatin; MEHD7945A; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2013
• First Posted: July 30, 2013
• Study Start: September 19, 2013
• Primary Completion: June 22, 2017
• Study Completion: June 22, 2017
• Last Updated: July 6, 2017

Record last verified: 2017-07

Locations

BE (3); US (3)